Hypoglycemic effects of grapefruit juice are well known but the effects of naringin, its main flavonoid on glucose intolerance and metabolic complications in type 1 diabetes are not known. To investigate the effects of naringin on glucose intolerance, oxidative stress and ketonemia in type 1 diabetic rats. Sprague-Dawley rats divided into 5 groups (n = 7) were orally treated daily with 3.0 ml/kg body weight (BW)/day of distilled water (group 1) or 50 mg/kg BW of naringin (groups 2 and 4, respectively). Groups 3, 4 and 5 were given a single intra-peritoneal injection of 60 mg/kg BW of streptozotocin to induce diabetes. Group 3 was further treated with subcutaneous insulin (4.0 IU/kg BW) twice daily, respectively. Stretozotocin (STZ) only-treated groups exhibited hyperglycemia, polydipsia, polyuria, weight loss, glucose intolerance, low fasting plasma insulin and reduced hepatic glycogen content compared to the control group. Furthermore they had significantly elevated Malondialdehyde (MDA), acetoacetate, β-hydroxybutyrate, anion gap and significantly reduced blood pH and plasma bicarbonate compared to the control group. Naringin treatment significantly improved Fasting Plasma Insulin (FPI), hepatic glycogen content, malondialdehyde, β-hydroxybutyrate, acetoacetate, bicarbonate, blood pH and anion gap but not Fasting Blood Glucose (FBG) compared to the STZ only-treated group. Naringin is not hypoglycemic but ameliorates ketoacidosis and oxidative stress. Naringin supplements could therefore mitigate complications of diabetic ketoacidosis.

Hyperlipidemia, a metabolic disorder of lipids, is a well known risk factor of cardiovascular events and metabolic syndrome. In this study, the in vivo lipid-lowering activity of the triterpene (Methyl-3β-hydroxylanosta-9,24-dien-21-oate), isolated from the stem bark of Protorhus longifolia, in high fat diet (HFD)-induced hyperlipidemic rats was investigated. Structure of the isolated compound was established and confirmed based on spectral (NMR, HRMS, IR) data analysis. Rats were divided into two groups; normal group (fed the normal commercial rats’ chow) and the HFD group. After 21 days of experimental period on their respective diets, the HFD rats were sub-divided into 4 groups of six rats per group. Two of the HFD groups were orally treated with the triterpene (100 and 200 mg/kg body weight) for 15 days. At the end of the experimental periods, the rats were sacrificed and blood samples were collected for biochemical assays. The results show that there were significant increases in total serum cholesterol (TC, 15.72 mmol/L) and low-density lipoprotein cholesterol (LDL-c, 7.41 mmol/L) with a reduction in high-density lipoprotein cholesterol (HDL-c, 14.75 mmol/L) in HFD-induced hyperlipidemic rats after 21 days. Oral administration of the triterpene (100 mg/kg.bw and 200 mg/kg.bw) for a period of 15 days resulted in significant lowering of the levels of TC (7.51 mmol/L) and LDL-c (4.46 mmol/L) with an increase in HDL-c (47.3 mmol/L) in HFD-induced hyperlipidemic rats. Significant decrease in atherogenic index and coronary risk index by the triterpene was observed in HFD-induced hyperlipidemic rats. The triterpene could effectively reduce or control the amount of serum cholesterol and LDL. It is apparent that the compound could contribute to new formulation with significant hypolipidemic effects.

Acyldepsipeptides (ADEPs) are a new class of emerging antimicrobial peptides (AMPs), which are currently explored for treatment of pathogenic infections, including tuberculosis (TB). These cyclic hydrophobic peptides have a unique bacterial target to the conventional anti-TB drugs, and present a therapeutic window to overcome Mycobacterium Tuberculosis (M. tb) drug resistance. ADEPs exerts their antibacterial activity on M. tb strains through activation of the protein homeostatic regulatory protease, the caseinolytic protease (ClpP1P2). ClpP1P2 is normally regulated and activated by the ClpP-ATPases to degrade misfolded and toxic peptides and/or short proteins. ADEPs bind and dysregulate all the homeostatic capabilities of ClpP1P2 while inducing non-selective proteolysis. The uncontrolled proteolysis leads to M. tb cell death within the host. ADEPs analogues that have been tested possess cytotoxicity and poor pharmacokinetic and pharmacodynamic properties. However, these can be improved by drug design techniques. Moreover, the use of nanomaterial in conjunction with ADEPs would yield effective synergistic effect. This new mode of action has potential to combat and eradicate the extensive multi-drug resistance (MDR) problem that is currently faced by the public health pertaining bacterial infections, especially TB.

The continuous rise in bacterial infections and antibiotic resistance is the driving force behind the search for new antibacterial agents with novel modes of action. Antimicrobial peptides (AMPs) have recently gained attention as promising antibiotic agents with the potential to treat drug-resistant infections. Several AMPs have shown a lower propensity towards developing resistance compared to conventional antibiotics. However, these peptides, especially acyldepsipeptides (ADEPs) present with unfavorable pharmacokinetic properties, such as high toxicity and low bioavailability. Different ways to improve these peptides to be drug-like molecules have been explored, and these include using biocompatible nano-carriers. ADEP1 analogues (SC005-8) conjugated to gelatin-capped Silver/Indium/Sulfide (AgInS₂) quantum dots (QDs) improved the antibacterial activity against Gram-negative (Escherichia coli and Pseudomonas aeruginosa), and Gram-positive (Bacillus subtilis, Staphylococcus aureus and Methicillin-resistant Staphylococcus aureus) bacteria. The ADEP1 analogues exhibited minimum inhibition concentrations (MIC) between 63 and 500 µM, and minimum bactericidal concentrations (MBC) values between 125 and 750 µM. The AgInS₂-ADEP1 analogue conjugates showed enhanced antibacterial activity as evident from the MIC and MBC values, i.e., 1.6–25 µM and 6.3–100 µM, respectively. The AgInS₂-ADEP1 analogue conjugates were non-toxic against HEK-293 cells at concentrations that showed antibacterial activity. The findings reported herein could be helpful in the development of antibacterial treatment strategies.