Non-alcoholic steatohepatitis (NASH), a type of non-alcoholic fatty liver disease, is characterized as steatosis and inflammation in the liver. NLRP3 inflammasome activation is associated with NASH pathology. We hypothesized that suppressing the NLRP3 inflammasome could be effective in preventing NASH. We searched substances that could inhibit the activation of the NLRP3 inflammasome and identified sweroside as an NLRP3 inhibitor. We investigated whether sweroside can be applied to prevent the pathological symptoms associated with NASH in a methionine–choline-deficient (MCD) diet-induced NASH mouse model. The activation of the NLRP3 inflammasome was determined by detecting the production of caspase-1 and IL-1β from pro-caspase-1 and pro-IL-1β in primary mouse macrophages and mouse liver. In a NASH model, mice were fed an MCD diet for two weeks with daily intraperitoneal injections of sweroside. Sweroside effectively inhibited NLRP3 inflammasome activation in primary macrophages as shown by a decrease in IL-1β and caspase-1 production. In a MCD diet-induced NASH mouse model, intraperitoneal injection of sweroside significantly reduced serum aspartate transaminase and alanine transaminase levels, hepatic immune cell infiltration, hepatic triglyceride accumulation, and liver fibrosis. The improvement of NASH symptoms by sweroside was accompanied with its inhibitory effects on the hepatic NLRP3 inflammasome as hepatic IL-1β and caspase-1 were decreased. Furthermore, sweroside blocked de novo synthesis of mitochondrial DNA in the liver, contributing to suppression of the NLRP3 inflammasome. These results suggest that targeting the NLRP3 inflammasome with sweroside could be beneficially employed to improve NASH symptoms.

As the global population ages, the prevalence of Parkinson’s disease (PD) is steadily on the rise. PD demonstrates chronic and progressive characteristics, and many cases can transition into dementia. This increases societal and economic burdens, emphasizing the need to find effective treatments. Among the widely recognized causes of PD is the abnormal accumulation of proteins, and autophagy dysfunction accelerates this accumulation. The resultant Lewy bodies are also commonly found in Alzheimer’s disease patients, suggesting an increased potential for the onset of dementia. Additionally, the production of free radicals due to mitochondrial dysfunction contributes to neuronal damage and degeneration. The activation of astrocytes and the M1 phenotype of microglia promote damage to dopamine neurons. The drugs currently used for PD only delay the clinical progression and exacerbation of the disease without targeting its root cause, and come with various side effects. Thus, there is a demand for treatments with fewer side effects, with much potential offered by natural products. In this study, we reviewed a total of 14 articles related to herbal medicines and natural products and investigated their relevance to possible PD treatment. The results showed that the reviewed herbal medicines and natural products are effective against lysosomal disorder, mitochondrial dysfunction, and inflammation, key mechanisms underlying PD. Therefore, natural products and herbal medicines can reduce neurotoxicity and might improve both motor and non-motor symptoms associated with PD. Furthermore, these products, with their multi-target effects, enhance bioavailability, inhibit antibiotic resistance, and might additionally eliminate side effects, making them good alternative therapies for PD treatment.

Alzheimer’s disease and Parkinson’s disease are the two most common neurodegenerative diseases in the world, and their incidence rates are increasing as our society ages. This creates a significant social and economic burden. Although the exact cause and treatment methods for these diseases are not yet known, research suggests that Alzheimer’s disease is caused by amyloid precursor protein, while α-synuclein acts as a causative agent in Parkinson’s disease. The accumulation of abnormal proteins such as these can lead to symptoms such as loss of protein homeostasis, mitochondrial dysfunction, and neuroinflammation, which ultimately result in the death of nerve cells and the progression of neurodegenerative diseases. The medications currently available for these diseases only delay their progression and have many adverse effects, which has led to increased interest in developing natural products with fewer adverse effects. In this study, we selected specific keywords and thesis content to investigate natural products that are effective in treating Alzheimer’s and Parkinson’s diseases. We reviewed 16 papers on natural products and found that they showed promising mechanisms of action such as antioxidant, anti-inflammatory, and mitochondrial function improvement. Other natural products with similar properties could also be considered potential treatments for neurodegenerative diseases, and they can be consumed as part of a healthy diet rather than as medicine.

Hyeonjin Kim, Soohyun Jeong, Sung Wook Kim, Hyung-Jin Kim, Dae Yong Kim, Tae Han Yook, Gabsik Yang. J Pharmacopuncture 2024;27:59-69. https://doi.org/10.3831/KPI.2024.27.2.59

Background: Monosodium urate crystal accumulation in the joints is the cause of gout, an inflammatory arthritis that is initiated by elevated serum uric acid levels. It is the most prevalent form of inflammatory arthritis, affecting millions worldwide, and requires effective treatments. The necessity for alternatives with fewer side effects is underscored by the frequent adverse effects of conventional therapies, such as urate-lowering drugs. IL-1β is a potential therapeutic target due to its significant role in the inflammatory response induced by MSU. Zanthoxylum piperitum Benn. (ZP), a shrub that possesses antibacterial, antioxidant, and anti-inflammatory properties, has demonstrated potential in the treatment of inflammatory conditions. Methods: For anti-inflammatory properties of ZP, Raw264.7 cell stimulated LPS were treated ZP and using RNA-seq with Bone marrow derived macrophage, we observed to change inflammatory gene. Pharmacological networks were conducted to select target gene associated with ZP. For in vivo, mice were injected MSU in footpad for induce gouty arthritis model. The components of ZP were analyzed using GC-MS, and distilled extracts of ZP (deZP) were prepared. Results: In vitro, deZP decreased inflammatory cytokines. However, in vivo, it also decreased paw thickness and IL-1β levels. The anti-inflammatory effects of deZP are believed to be mediated through the NLRP3 inflammasome pathway, as indicated by RNA sequencing and network pharmacology analyses. Conclusions: ZP has an anti-inflammatory effect and regulation of the NLRP3 inflammasome in vitro and in vivo. Further research, including clinical trials, is required to confirm the safety of deZP, determine the optimal dosing, and evaluate its long-term effects.

Sung Wook Kim, Jun Ho Lee, Hyeonjin Kim, Seong Hoon Lee, Dajeong Jeong, Hyuk Soon Kim, Cheol-Jung Lee, Dae Yong Kim, Tae Han Yook, Gabsik Yang. J Pharmacopuncture 2022;25:396-403. https://doi.org/10.3831/KPI.2022.25.4.396