Acute pancreatitis (AP) is an inflammatory disorder, involving acinar cell death and the release of inflammatory cytokines. Currently, there are limited effective therapeutic agents for AP. Betulinic acid (BA) is a pentacyclic triterpenoid extracted from Betula platyphylla that has been shown to have anti-inflammatory effects. In this study, we aimed to investigate the effects of BA on AP and elucidate the potential underlying mechanisms. AP was induced in mice through six intraperitoneal injections of cerulein. After the last cerulein injection, the mice were sacrificed. Our results revealed that pre- and post-treatment with BA significantly reduced the severity of pancreatitis, as evidenced by a decrease in histological damage in the pancreas and lung, serum amylase and lipase activity and pancreatic myeloperoxidase activity. Furthermore, BA pretreatment reduced proinflammatory cytokine production, augmentation of chemokines, and infiltration of macrophages and neutrophils in the pancreas of AP mice. In addition, mice that were pretreated with BA showed a reduction in Iκ-Bα degradation and nuclear factor-kappa B (NF-κB) binding activity in the pancreas. Moreover, BA reduced the production of proinflammatory cytokines and NF-κB activation in pancreatic acinar cells (PACs). These findings suggest that BA may have prophylactic and therapeutic effects on AP via inhibition of the NF-κB signaling pathway.

Cannabis sativa L. has been widely used by humans for centuries for various purposes, such as industrial, ceremonial, medicinal, and food. The bioactive components of Cannabis sativa L. can be classified into two main groups: cannabinoids and terpenes. These bioactive components of Cannabis sativa L. leaf and inflorescence extracts were analyzed. Mice were systemically administered 30 mg/kg of Cannabis sativa L. leaf extract 1 h before lipopolysaccharide (LPS) administration, and behavioral tests were performed. We conducted an investigation into the oxygen saturation, oxygen tension, and degranulation of mast cells (MCs) in the deep cervical lymph nodes (DCLNs). To evaluate the anti-inflammatory effect of Cannabis sativa L. extracts in BV2 microglial cells, we assessed nitrite production and the expression levels of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α. The main bioactive components of the Cannabis sativa L. extracts were THCA (a cannabinoid) and β-caryophyllene (a terpene). Cannabis sativa L. leaf extract reduced the immobility time in the forced swimming test and increased sucrose preference in the LPS model, without affecting the total distance and time in the center in the open field test. Additionally, Cannabis sativa L. leaf extract improved oxygen levels and inhibited the degranulation of MCs in DCLNs. The Cannabis sativa L. extracts inhibited IL-1β, IL-6, TNF-α, nitrite, iNOS, and COX-2 expression in BV2 microglia cells. The efficacy of Cannabis sativa L. extracts was suggested to be due to the entourage effect of various bioactive phytochemicals. Our findings indicate that these extracts have the potential to be used as effective treatments for a variety of diseases associated with acute inflammatory responses.

Background/Objectives: Neurodegenerative disorders have emerged as a major global public health concern, and the burden is predicted to increase over time. Modulating neuroinflammation and microglial activity is considered a promising target for improving neurodegenerative disorders. The leaf of honeysuckle (LH), which has anti-inflammatory properties, has long been collected, regardless of the season, and used for medicinal purposes. However, research on its effects on neuroinflammation is scarce. In this study, we determined the neuroprotective effects of LH water extract by inhibiting microglial activation induced by lipopolysaccharide (LPS). Methods: The production or secretion of pro-inflammatory mediators was examined in LPS-exposed BV2 cells to ascertain the efficacy of LH water extract in improving neuroinflammation. In addition, the phosphorylation of mitogen-activated protein kinases (MAPKs) and the degradation of inhibitory κBα (IκBα) were analyzed to elucidate the regulatory mechanisms of LH water extract. Ultra-performance liquid chromatography (UPLC) analysis was conducted to identify the active component of the LH. Results: LH water extract suppressed the formation of inducible nitric oxide synthase (iNOS), nitric oxide (NO), and pro-inflammatory cytokines, including interleukin (IL)-1β and tumor necrosis factor (TNF)-α, in LPS-activated BV2 cells. LH impeded the activation of c-Jun N-terminal kinase (JNK). Moreover, chlorogenic acid was found in LH. Conclusions: The above findings suggest that LH water extract could improve neuroinflammation.

Background: Lipopolysaccharide (LPS)-induced neuroinflammation is a well-established model for studying depression-like behavior, driven by pro-inflammatory cytokines such as TNF-α and IL-1β. Mast cells (MCs) contribute to neuroinflammation by releasing mediators that exacerbate depressive-like symptoms. This study evaluates the antidepressant-like and anti-inflammatory effects of Cannabis sativa L. inflorescence extract (CSL) in an LPS-induced neuroinflammation model. Methods: Male C57BL/6 mice were intraperitoneally injected with CSL at doses of 10, 20, and 30 mg/kg, 30 min prior to LPS (0.83 mg/kg) administration. Depressive behaviors were assessed using the sucrose preference test (SPT), tail suspension test (TST), and forced swimming test (FST). The neutrophil-to-lymphocyte ratio (NLR) was measured to assess systemic inflammation. Cytokine levels in the prefrontal cortex (PFC) were measured, and mast cell degranulation in the lymph nodes and dura mater was analyzed histologically (approval number: WKU24-64). Results: CSL significantly improved depressive-like behaviors and decreased the NLR, indicating reduced systemic inflammation. CSL also significantly reduced TNF-α and IL-1β levels in the PFC. Furthermore, CSL inhibited MC degranulation in the deep cervical lymph nodes and dura mater, with the strongest effects observed at 30 mg/kg. Conclusions: CSL demonstrated antidepressant-like and anti-inflammatory effects in an LPS-induced neuroinflammation model, likely through the modulation of cytokine expression and mast cell activity. These results suggest the potential of CSL as a therapeutic option for treating inflammation-related depression.

Arecae pericarpium (AP), the fruit peel of the betel palm, is a traditional Oriental herbal medicine. AP is used to treat various diseases and conditions, such as ascites, edema, and urinary retention, in traditional Korean medicine. Recent studies have demonstrated its anti-obesity and antibacterial effects; however, its anti-neuroinflammatory effects have not yet been reported. Therefore, we investigated the anti-neuroinflammatory effects of AP on lipopolysaccharide (LPS)-stimulated mouse microglia in this study. To determine the anti-neuroinflammatory effects of AP on BV2 microglial cells, we examined the production of nitric oxide (NO) using Griess assay and assessed the mRNA expression levels of inflammatory mediators, such as inducible NO synthase (iNOS) and cyclooxygenase (COX)-2, and pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α, using a real-time reverse transcription-polymerase chain reaction. Furthermore, we determined the levels of mitogen-activated protein kinases and IκBα via Western blotting to understand the regulating mechanisms of AP. AP treatment decreased NO production in LPS-stimulated BV2 cells. Additionally, AP suppressed the expression of iNOS and COX-2 and the production of pro-inflammatory cytokines. AP also inhibited the activation of p38 and nuclear factor-kappa B (NF-κB) in LPS-stimulated BV2 cells. Therefore, AP exerts anti-neuroinflammatory effects via inactivation of the p38 and NF-κB pathways.

Acute kidney injury (AKI) is a major side effect of cisplatin, a crucial anticancer agent. Therefore, it is necessary to develop drugs to protect against cisplatin-induced nephrotoxicity. Ojeoksan (OJS), a traditional blended herbal prescription, is mostly used in Korea; however, there are no reports on the efficacy of OJS against cisplatin-induced AKI. To investigate the reno-protective effect of OJS on AKI, we orally administered 50, 100, and 200 mg/kg of OJS to mice 1 h before intraperitoneal injection with 20 mg/kg of cisplatin. OJS inhibited the increase of blood urea nitrogen (BUN) and serum creatinine (SCr) levels and reduced histological changes in the kidney, like loss of brush borders, renal tubular necrosis, and cast formation. Administration of OSJ reduced the levels of pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α. In addition, OJS inhibited the mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) pathways in cisplatin-induced AKI. These results suggest that OJS attenuates cisplatin-induced AKI by downregulating the MAPK and NF-κB pathways.