Neuroinflammation, which is mediated by microglia that release various inflammatory cytokines, is a typical feature of neurodegenerative diseases (NDDs), such as Alzheimer’s disease and Parkinson’s disease. Hence, alleviating neuroinflammation by downregulating pro-inflammatory action, and upregulating anti-inflammatory action of microglia is an efficient therapeutic target for NDDs. In this study, we evaluated whether trichosanthis semen (TS), a dried ripe seed of Trichosanthes kirilowii Maximowicz, reduces lipopolysaccharide (LPS)-induced neuroinflammation by regulating microglial responses in vitro and in vivo. Our results presented that TS reduced the release of pro-inflammatory mediators, such as nitric oxide (NO), inducible NO synthase, tumor necrosis factor-α, interleukin-1β, and interleukin-6 via inhibition of the nuclear factor kappa B (NF-κB) signaling pathway in LPS-treated BV2 microglial cells. Moreover, TS induced anti-inflammatory mediators, such as interleukin-10, found in inflammatory zone 1, and chitinase 3-like 3 by the upregulation of heme oxygenase 1 (HO-1). We further confirmed that TS administration suppressed microglial activation, but enhanced HO-1 expression in LPS-injected mice. These results suggest that TS has anti-neuroinflammatory effects via inhibition of NF-κB signaling through the activation of HO-1, and that TS may be a therapeutical candidate for NDDs treatment.

Neuroinflammation, a key pathological contributor to various neurodegenerative diseases, is mediated by microglial activation and subsequent secretion of inflammatory cytokines via the mitogen-activated protein kinase (MAPK) signaling pathway. Moreover, neuroinflammation leads to synaptic loss and memory impairment. This study investigated the inhibitory effects of PNP001, a mixture of Trichosanthis Semen and Zingiberis Rhizoma in a ratio of 3:1, on neuroinflammation and neurological deficits induced by lipopolysaccharide (LPS). For the in vitro study, PNP001 was administered in LPS-stimulated BV2 microglial cells, and reduced the pro-inflammatory mediators, such as nitric oxide, inducible nitric oxide synthase, and cyclooxygenase-2 by downregulating MAPK signaling. For the in vivo study, ICR mice were orally administered PNP001 for 18 consecutive days, and concurrently treated with LPS (1 mg/kg, i.p.) for 10 days, beginning on the 4th day of PNP001 administration. The remarkably decreased number of activated microglial cells and increased expression of pre- and post-synaptic proteins were observed more in the hippocampus of the PNP001 administered groups than in the LPS-treated group. Furthermore, daily PNP001 administration significantly attenuated long-term memory decline compared with the LPS-treated group. Our study demonstrated that PNP001 inhibits LPS-induced neuroinflammation and its associated memory dysfunction by alleviating microglial activation and synaptic loss.

Background/Objectives: Parkinson’s disease (PD) is a common neurodegenerative disease characterized by motor symptoms caused by the loss of dopaminergic neurons. While the pathophysiology of PD is still not fully understood, it is recognized that oxidative stress plays a major role in its progression. Previous studies have shown that the aerial parts of Artemisia iwayomogi Kitamura (AIK) possess medicinal properties, including antioxidant activity. This study aimed to investigate whether AIK can alleviate neuronal loss and motor symptoms in a PD model and to explore its therapeutic mechanisms. Methods: For the in vitro study, PC12 cells were treated with AIK and 1-methyl-4-phenylpyridinium (MPP⁺). For the in vivo study, C57BL/6J mice were orally administered AIK for 12 days; they received intraperitoneal injections of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 5 consecutive days, starting on the 8th day of AIK administration. Results: AIK treatment to PC12 cells in the presence of MPP⁺ enhanced the phosphorylation of the protein kinase B/glycogen synthase kinase-3β signaling pathway, which is a crucial regulator of nuclear factor erythroid 2-related factor 2 (Nrf2) translocation. Additionally, AIK treatment increased cell survival and induced an antioxidant response involving heme oxygenase-1, via increasing the level of Nrf2 in the nucleus. In an MPTP-induced mouse model of PD, AIK administration activated Nrf2 in dopaminergic neurons and prevented the loss of dopaminergic neurons in the brain, which in turn alleviated motor dysfunction. Conclusions: Collectively, these findings suggest that AIK is a potential botanical candidate for PD treatment by protecting dopaminergic neurons through antioxidant activity.

Fracture healing is a multistage regenerative process requiring the coordinated regulation of inflammation, osteogenesis, and bone remodeling, yet pharmacological agents that effectively modulate these processes remain limited. Adenophorae Radix (AR), a traditional medicinal herb used for tissue repair, has not been mechanistically investigated in skeletal regeneration. In this study, a mouse femoral fracture model was employed to evaluate the effects of short-term (7 days) and long-term (5 weeks) oral administration of AR. Bone regeneration was assessed using micro-computed tomography, histological staining, and quantitative real-time polymerase chain reaction. Network pharmacology and molecular docking were applied to predict bioactive AR constituents and their target pathways, followed by in vivo validation. Short-term AR treatment significantly upregulated osteogenic markers, including RUNX2 and osteocalcin, in the bone marrow, indicating early activation of osteoblast differentiation. Long-term administration enhanced bone mineral density, trabecular organization, and callus maturation. Network pharmacology analysis identified cycloartenol acetate, β-sitosterol, and mandenol as major active compounds targeting osteogenesis- and osteoclast-related pathways, converging on HIF1A, PTGS2, and PPARG. Molecular docking demonstrated strong binding affinities between these compounds and their predicted targets, which was supported by increased expression of HIF1A, PTGS2, and PPARG in AR-treated femora. Collectively, these findings suggest that AR promotes fracture healing by regulating osteogenic differentiation and bone remodeling through multi-target transcriptional networks.