Insulin resistance is a hallmark of type 2 diabetes mellitus (T2DM) and the underlying cause of various metabolic changes observed in type 2 diabetic patients. This study investigated the molecular basis of the anti-hyperglycemic activity of the lanosteryl triterpene (RA-3), from Protorhus longifolia stem bark, in hyperlipidemic and streptozotocin (STZ)-induced T2DM in rats. The high-fat diet fed (HFD) and STZ-induced T2DM in rat model was used to evaluate the anti-hyperglycemic activity of RA-3. The hyperlipidemic rats received a single intraperitoneal injection of STZ (35 mg/kg body weight) to induce T2DM. The experimental animals received a daily oral single dose of RA-3 (100 mg/kg body) for a period of 28 days, whiles the control group received distilled water only. The animals were euthanized, and skeletal muscle was collected for protein (IRS-1, AKT, GSK and GLUT 4) expression analysis. Western blot confirmed expression of the proteins. Treatment of the diabetic animals with the RA-3 showed marked reduction in fasting plasma glucose levels in comparison to the untreated diabetic group animals. A significant decrease in p-GSK-3β and p-AKT expression was observed, whereas the expression of IRS-1ser307 were increased when compared to the diabetic control group. This effect was ablated upon treatment with RA-3 and this was concomitant to an observed increase in GLUT 4 expression. The results obtained in the present study strongly suggested that the anti-hyperglycemic effect of RA-3 could partly be associated with its ability to improve cellular glucose uptake in muscle tissue from T2DM.

The increasing incidence of hypercholesterolemia-related diseases even in the presence of the currently available cholesterol-lowering drugs indicates a need to discover new therapeutic drugs. This study aimed to investigate the hypocholesterolemic potential of two triterpenoids isolated from Protorhus longifolia stem bark. In silico techniques and in vitro enzyme assays were used to evaluate the potential inhibition of cholesterol esterase and HMG-CoA reductase by the triterpenoids (ARM-2 and RA-5). The toxicity, modulation of low-density lipoprotein (LDL) uptake, and associated gene expression were determined in HepG2 hepatocytes. In silico molecular docking revealed that ARM-2 compared with RA-5 has a relatively stronger binding affinity for both enzymes. Both triterpenoids further demonstrated promising in silico drug-likeness properties and favorable ADMET profiles characterized by high intestinal absorption and lack of CYP450 enzyme inhibition. The compounds further showed, to varying degrees of efficacy, inhibition of cholesterol micellization as well as both cholesterol esterase and HMG-CoA reductase activities with IC₅₀ values ranging from 16.4 to 41.1 μM. Moreover, enhanced hepatic cellular LDL uptake and the associated upregulation of the LDL-R and SREBP-2 gene expression were observed in the triterpenoid-treated HepG2 cells. It is evident that the triterpenoids, especially ARM-2, possess hypocholesterolemic properties, and these molecules can serve as leads or structural templates for the development of new hypocholesterolemic drugs.

A substantial literature supports antidiabetic properties of the lanosteryl triterpene (methyl-3β-hydroxylanosta-9,24-dien-21-oate, RA-3) isolated from Protorhus longifolia stem bark. However, the molecular mechanism(s) associated with the antihyperglycemic properties of the triterpene remained to be explored. The current study aimed at investigating the molecular mechanism(s) through which RA-3 improves insulin signaling in streptozotocin-induced type 1 diabetic rats. The type 1 diabetic rats were treated daily with a single oral dose of RA-3 (100 mg/kg) for 28 days. The rats were then sacrificed, and blood, skeletal muscle and pancreases were collected for biochemical, protein expression and histological analysis, respectively. Persistently high blood glucose levels in the diabetic control rats significantly increased expression of IRS-1Ser307 while the expression of p-Akt Ser473, p-GSK-3β Ser9, GLUT 4 and GLUT 2 were decreased. However, enhanced muscle insulin sensitivity, which was indicated by a decrease in the expression of IRS-1ser307 with a concomitant increase in the p-AktSer473, p-GSK-3β Ser9, GLUT 4 and GLUT 2 expression were observed in the diabetic rats treated with RA-3. The triterpene-treated animals also showed an improved pancreatic β-cells morphology, along with increased C-peptide levels. An increase in the levels of serum antioxidants such as catalase, superoxide dismutase, and reduced glutathione was noted in the rats treated with the triterpene, while their serum levels of interleukin-6 and malondialdehyde were reduced. It is apparent that RA-3 is able to improve the insulin signaling in type 1 diabetic rats. Its beta (β)-cells protecting mechanism could be attributed to its ability to alleviate inflammation and oxidative stress in the cells.

The emergence of a new mpox sub-clade Ib and changes in transmission pattern are of concern. To inform strategies to protect populations and improve outcomes, we implemented a rapid research needs appraisal (RRNA) to identify existing evidence on mpox clade I. We searched Embase, MEDLINE, Scopus, and grey literature to 11 February 2025 for human mpox clade I studies. Of 79 studies identified, 2.5% (2/79) were interventional, 97.4% (77/79) observational, presenting data on 59,183 mpox cases. Most (57/79) focused on clade Ia, 16/79 clade Ib, and 6/79 unspecified sub-clade I. 90.8% were set in Africa. Studies focused on clinical characteristics (n = 55), transmission (n = 23), risk factors for disease/severe disease (n = 13), diagnostics (n = 9), social/behavioural factors (n = 6), immune response/seroprevalence (n = 5), and vaccine/treatments (n = 4). Symptoms and complications were similar for both sub-clades. Three studies reported foetal death in 8/12-8/14 pregnant women infected with clade Ib and in 3/4 of women with clade Ia. The pooled case fatality rate (CFR) was 6% (95% CI 3% to 8%) in clade Ia studies and 1% (95% CI 0% to 1%) in clade Ib studies. There were no studies on effectiveness of prevention, treatment, risk of asymptomatic infection, or immune protection over time. The identified evidence-gaps provide a baseline to inform coordinated research strategies to generate evidence for clinical and public health responses to improve outcomes.