The Clp/Hsp100 family, part of the ATPase associated with various cellular activities (AAA+) superfamily, includes caseinolytic peptidase B (ClpB), a highly conserved protein found in bacteria, fungi, protozoa, and plants. Notably, ClpB is present in all ESKAPE pathogens: Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp. ClpB plays a crucial role in reactivating and disaggregating proteins, enabling pathogens to survive under host-induced stress and conferring thermotolerance to bacterial cells. Infections caused by ESKAPE pathogens are particularly challenging due to their resistance to broad-spectrum antibiotics and biofilm formation, posing a significant global health threat as they are often multidrug-resistant, extensively drug-resistant, and pan-drug-resistant. Given its absence in human cells and its essential role in bacterial survival under stress, ClpB is a promising target for antimicrobial therapy. Targeting Hsp100 family proteins could lead to the development of novel antifungal and antiprotozoal treatments. This review explores the function of ClpB in the survival of ESKAPE pathogens and the protozoan Plasmodium falciparum. Relevant research findings were compiled using academic databases, and data analysis was performed using Clustal Omega Multiple Sequence Alignment and Boxshade tools.
Objective: To investigate the effects of Alpiniae oxyphyllae Fructus (AOF) on renal lipid deposition in diabetic kidney disease (DKD) and elucidate its molecular mechanisms.
Methods: The mechanism of AOF in treating DKD was explored by network pharmacological enrichment analysis, molecular docking, and molecular dynamics simulation. The effects of AOF on renal function and lipid deposition were assessed in a mouse model of DKD and high glucose-stressed HK-2 cells. Cell viability and lipid accumulation were detected by CCK8 and oil red O staining. The expressions of PPARα and fatty acid oxidation-related genes (ACOX1 and CPT1A) were detected by quantitative RT-PCR, Western blot, and immunofluorescence. Furthermore, PPARα knockdown was performed to examine the molecular mechanism of AOF in treating DKD.
Results:Network pharmacological enrichment analysis, molecular docking, and molecular dynamics simulation showed that the active compounds in AOF targeted PPARα and thus transcriptionally regulated ACOX1 and CPT1A. AOF lowered blood glucose, improved dyslipidemia, and attenuated renal injury in DKD mice. AOF-containing serum accentuated high glucose-induced decrease in cell viability and ameliorated lipid accumulation. Additionally, it significantly upregulated the expression of PPARα, ACOX1, and CPT1A in both in vivo and in vitro experiments, which was reversed by PPARα knockdown.
Conclusions: AOF may promote fatty acid oxidation via PPARα to ameliorate renal lipid deposition in DKD.
Objective: To investigate the effect of Rosa moschata (R. moschata) extract on haloperidol-induced Parkinson’s disease (PD) in rats.
Methods: Haloperidol (1 mg/kg) was given to rats intraperitoneally for 3 weeks for induction of PD. R. moschata extract (150, 300 and 600 mg/kg) was administered orally for 21 days. The neuroprotective role of R. moschata leaf extract in PD was explored by performing neurobehavioral tests and RT-PCR analysis and measuring neurotransmitters and oxidative stress biomarkers.
Results: An improvement in motor functions and muscle strength was observed in PD rats treated with R. moschata extract. The levels of dopamine, serotonin, noradrenaline, superoxide dismutase, catalase, glutathione, and superoxide dismutase were significantly increased (P < 0.001), whereas acetylcholinesterase and malondialdehyde levels were markedly decreased by treatment with R. moschata extract (P < 0.001). The extract also markedly downregulated the mRNA expressions of IL-1β, α-synuclein, IL-1α, and TNF-α in brain tissue. Moreover, histopathological analysis indicated that neurofibrillary tangles and plaques were noticeably decreased in a dose-dependent manner in PD rats treated with R. moschata extract.
Conclusions: R. moschata extract alleviates haloperidol-induced PD in rats by reducing oxidative stress and neurodegeneration. It may be used for management and treatment of PD. However, additional studies are required to confirm its efficacy and molecular mechanisms.
Objective: To assess the protective effects of trigonelline against spinal cord injury (SCI) in rats.
Methods: Rats (Sprague-Dawley, male) were randomly assigned to seven groups (n=15 per group): normal, sham, SCI control (1% DMSO), methylprednisolone (30 mg/kg), and trigonelline (50, 100, and 200 mg/kg). Rats received respective treatment daily for 28 days. SCI was induced by using a temporary aneurysm clip. Behavioral, biochemical, and histological analyses were performed to investigate the neuroprotective effect of trigonelline.
Results: Trigonelline (100 and 200 mg/kg) treatment effectively (P<0.05) mitigated SCI-induced changes in mechano-tactile sensation, allodynia, hyperalgesia, and motor nerve conduction velocity. It notably (P<0.05) downregulated apoptotic (Bax and caspase-3) and inflammatory (COX-II) markers, while upregulating Bcl-2 and BDNF mRNA expression in the spinal cord (P<0.05). Furthermore, trigonelline effectively alleviated (P<0.05) SCI-induced alterations in mitochondrial complex levels, resulting in enhanced nicotinamide adenine dinucleotide dehydrogenase, succinate dehydrogenase, redox activity, and cytochrome-C levels. Histological examination of spinal cord tissue indicated that trigonelline significantly (P<0.05) ameliorated the histological damage caused by SCI, thereby improving neuronal degeneration, inflammatory cell infiltration, and necrosis.
Conclusions: Trigonelline shows neuroprotective properties in SCI rats by reducing allodynia, hyperalgesia, and inflammation, stabilizing mitochondrial enzyme complexes, and modulating apoptotic and neurotrophic factors. Thus, trigonelline holds promise as a potential neuroprotective agent.