Gifu Pharmaceutical University

Pontederia vaginalis Burm. f. is an aquatic plant widely distributed in East and Southeast Asia, where its young leaves and stems are traditionally consumed. Despite its regional use as a food source, the phytochemical constituents of this species have remained largely unexplored. In particular, it has not been determined whether P. vaginalis contains phenylphenalenone-type compounds, which are known from related species such as P. crassipes (syn. Eichhornia crassipes). In this study, phytochemical investigation on P. vaginalis led to the isolation of two novel diallylheptanoids-pontevagonols A (1) and B (2)-as well as a naturally occurring phenylphenalenone, 2-hydroxy-4-methoxy-9-phenylphenalen-1-one (3), and eight known phenolic derivatives. This represents the first report of these compound types from P. vaginalis, and clarifies the phenolic composition of the Pontederiaceae family.

Photoreceptor cells in the retina are highly specialized sensory cells that function as light receptors. During the conversion of light into neural signals, photoreceptors are constantly exposed to oxidative stress. Although environmental stressors, such as excessive light exposure, have been implicated in the progression of various retinal diseases, including dry age-related macular degeneration (AMD), the molecular mechanisms underlying the light-induced stress response remain incompletely elucidated. Excessive light exposure triggers the endoplasmic reticulum (ER) stress response in cells and also induces mitochondrial dysfunction characterized by depolarization and fragmentation, ultimately leading to cell death. We have shown that compounds derived from natural products, such as delphinidins and pentadecyl, exert protective effects against blue light-induced cellular damage. Furthermore, crocetin, a natural carotenoid pigment, has been shown to suppress ultraviolet-A (UV-A)-induced mitochondrial fragmentation in corneal epithelial cells. In this review, we provide an overview of light stress-induced injuries to intracellular membrane organelles, particularly mitochondria and the ER, and the cellular response mechanisms that are mediated through these organelles. These findings suggest that maintaining the homeostasis of intracellular membrane organelles represents an important therapeutic target for the prevention and treatment of retinal degenerative diseases.

Whether cholinergic activity in the septohippocampal network affects cognitive dysfunction via hippocampal cholinergic neurostimulating peptide (HCNP) in Alzheimer's pathogenesis remains unclear.

An Alzheimer's pathogenesis by mutation in amyloid‐beta precursor protein gene ( App NL‐G‐F ) knock‐in (KI) and HCNP precursor protein conditional knockout (HCNP‐pp cKO) mouse model was generated, exhibiting both cholinergic dysfunction and amyloid pathogenesis. Theta power‐related cholinergic function and long‐term potentiation (LTP) were evaluated in App NL‐G‐F KI/HCNP‐pp cKO mice. Molecules associated with the cholinergic/glutamatergic neurons, amyloid beta (Aβ), and inflammation were examined.

Reduced HCNP levels enhanced cognitive impairment, inhibiting theta power and LTP, although without accompanying pathological changes or inflammation. Decreased N ‐methyl‐D‐aspartate receptor subunit 2A (NR2A), choline acetyltransferase (ChAT), and Vesicular acetylcholine transporter (VAChT) levels were observed in the hippocampus and ChAT in the medial septal nucleus (MSN) of App NL‐G‐F KI/HCNP‐pp cKO mice.

Cholinergic dysfunction in HCNP‐pp cKO mice exacerbates cognitive dysfunction in App NL‐G‐F KI mice. The obtained mouse models are expected to be used to investigate cholinergic dysfunction and amyloid pathogenesis in AD.