Aronia melanocarpa, known as black chokeberry, is rich in polyphenols, comprising flavonoids, such as anthocyanins, flavanols, and flavonols, and phenolic acids, such as chlorogenic acid. These polyphenols endow Aronia melanocarpa with preventive and therapeutic properties against various human diseases. Aronia melanocarpa has beneficial effects against diseases such as diabetes, inflammation, and hypertension. Considering the diverse functional components of Aronia melanocarpa, its efficacy in disease prevention and treatment can operate through multiple pathways, offering a more robust approach to disease control. This review covers the latest research results on the functional components of Aronia melanocarpa and their effects on human diseases.

Prostaglandin E₂ (PGE₂) is known to be effective in regenerating tissues, and bimatoprost, an analog of PGF_2α, has been approved by the FDA as an eyelash growth promoter and has been proven effective in human hair follicles. Thus, to enhance PGE₂ levels while improving hair loss, we found dihydroisoquinolinone piperidinylcarboxy pyrazolopyridine (DPP), an inhibitor of 15-hydroxyprostaglandin dehydrogenase (15-PGDH), using DeepZema^®, an AI-based drug development program. Here, we investigated whether DPP improved hair loss in human follicle dermal papilla cells (HFDPCs) damaged by dihydrotestosterone (DHT), which causes hair loss. We found that DPP enhanced wound healing and the expression level of alkaline phosphatase in DHT-damaged HFDPCs. We observed that DPP significantly down-regulated the generation of reactive oxygen species caused by DHT. DPP recovered the mitochondrial membrane potential in DHT-damaged HFDPCs. We demonstrated that DPP significantly increased the phosphorylation levels of the AKT/ERK and activated Wnt signaling pathways in DHT-damaged HFDPCs. We also revealed that DPP significantly enhanced the size of the three-dimensional spheroid in DHT-damaged HFDPCs and increased hair growth in ex vivo human hair follicle organ culture. These data suggest that DPP exhibits beneficial effects on DHT-damaged HFDPCs and can be utilized as a promising agent for improving hair loss.

Diabetic foot ulcers represent a severe complication of diabetes, often resulting in amputation and high mortality rates. Currently, there are no treatments for diabetic foot ulcers other than antibiotics and dressings. In this study, we evaluated the wound-healing effects of an antidiabetic agent pinitol in lipopolysaccharide (LPS)-damaged human dermal fibroblasts (HDFs) and streptozotocin (STZ)-induced diabetic rat models with a foot wound. Our findings indicated that pinitol enhanced cell migration, proliferation, and wound healing by activating Nrf2, thereby mitigating oxidative stress and inflammatory responses at the wound site. Additionally, pinitol restored mitochondrial energy metabolism, decreased matrix metalloproteinase (MMP) activity, and increased collagen deposition. Furthermore, pinitol facilitated angiogenesis, contributing to improved wound healing. Taken together, these findings suggest that pinitol could be a promising therapeutic agent for the treatment of diabetic foot ulcers.

Hair loss is often associated with oxidative stress and mitochondrial dysfunction in human follicle dermal papilla cells (HFDPCs), resulting in impaired cellular function and follicle degeneration. Thus, many studies have been conducted on natural plants aimed at inhibiting hair loss. This study investigated the therapeutic potential of exosomes derived from the rhizomes of Iris germanica L. (Iris-exosomes) in HFDPCs damaged by dihydrotestosterone (DHT). Iris-exosomes significantly reduced reactive oxygen species (ROS) levels, restoring mitochondrial membrane potential and ATP production, thereby mitigating oxidative stress and improving mitochondrial function. These effects occurred alongside enhanced cellular processes critical for hair follicle regeneration, including increased cell migration, alkaline phosphatase (ALP) activity, and three-dimensional (3D) spheroid formation, which replicates the follicle-like microenvironment and promotes inductive potential. Furthermore, Iris-exosomes stimulated the Wnt/β-catenin signaling pathway by enhancing glycogen synthase kinase-3β (GSK-3β), AKT, and extracellular signal-regulated kinase (ERK), leading to β-catenin stabilization and nuclear translocation, thereby supporting the expression of genes essential for hair growth. Taken together, these findings suggest that Iris-exosomes can be promising ingredients for alleviating hair loss.

Prostaglandin D₂ (PGD₂) levels are high in the balding areas of human scalps, and PGD₂ has been found to inhibit hair growth. It is known that the inhibition of the PGD₂ receptor can promote hair growth by preventing hair follicles from entering the catagen phase. Thus, we identified an antagonist of DP2, the receptor for PGD2, as a potential treatment for hair loss using an AI-based DeepZema^® drug development program. In this study, we identified that the DP₂ antagonist (DP2A) could ameliorate alopecia in human follicle dermal papilla cells (HFDPCs) that were stimulated by dihydrotestosterone (DHT), a known molecule related to hair loss. We observed that the DP2A promoted wound healing efficiency and increased alkaline phosphatase levels in the HFDPCs that were damaged with DHT. In addition, we found that the DP2A diminished the reactive oxygen species (ROS) levels generated in the DHT-damaged HFDPCs. We confirmed that the DP2A effectively recovered the membrane potential of mitochondria in these cells. We also demonstrated that the DP2A enhanced the phosphorylation levels of both Akt and ERK in the HFDPCs that were damaged with DHT. Notably, we revealed that the DP2A slightly enlarged the three-dimensional spheroid size in these cells and confirmed that the DP2A improved hair growth in the organ culture of human hair follicles. Taken together, we suggest that DP2A has therapeutic effects on HFDPCs that are damaged by DHT and holds promise as a potential treatment for treating hair loss.

3-O-Methyl-D-chiro-inositol (pinitol) has been reported to possess insulin-like effects and is known as one of the anti-diabetic agents for improving muscle and liver function. However, the beneficial effects of pinitol on human dermal microvascular endothelial cells (HDMECs) are not well understood. In this study, we investigated whether pinitol could protect HDMECs from damage induced by lipopolysaccharides (LPSs), which cause various cell defects. We observed that pinitol enhanced wound healing for LPS-damaged HDMECs. We found that pinitol significantly downregulated the LPS-induced upregulation of reactive oxygen species (ROS). Pinitol also significantly restored the mitochondrial membrane potential in these cells. Immunofluorescence analysis revealed that pinitol notably reduced the nuclear localization of NF-κB in LPS-damaged HDMECs. Furthermore, we demonstrated that pinitol decreased the phosphorylation levels of the MAPK family in LPS-damaged HDMECs. Interestingly, we observed that pinitol improved tube formation in LPS-damaged HDMECs. Taken together, we suggest that pinitol exerts several beneficial effects on LPS-damaged HDMECs and may be a promising therapeutic agent for improving vascular-related skin diseases.