Oleic acid (OA) is released from brain phospholipids after cerebral ischaemia; however, its role in ischaemic injury remains unknown. We hypothesised that OA has neuroprotective effects after cerebral ischaemia, which may be exerted through peroxisome proliferator-activated receptor gamma (PPAR-γ) activation, since OA is an endogenous ligand of PPAR-γ. The effects of OA administration were evaluated in rodent models of middle cerebral artery occlusion (MCAO), photothrombosis, and four-vessel occlusion (4-VO). We determined the time window of therapeutic opportunity and examined the ability of the PPAR-γ antagonist GW9662 to reverse OA’s protective effects after MCAO. We found that OA administration decreased the MCAO-induced infarct volume and functional deficits, photothrombosis-induced infarct volume, and 4-VO-induced hippocampal neuronal death. Additionally, OA was highly efficacious when administered up to 3 h after MCAO. Pre-treatment with GW9662 abolished the inhibitory effects of OA on the infarct volume and immunoreactivity of key inflammatory mediators in the ischaemic cortex. Our results indicate that OA has neuroprotective effects against transient and permanent focal cerebral ischaemia, as well as global cerebral ischaemia. It may have therapeutic value for the ischaemic stroke treatment with a clinically feasible therapeutic window. The OA-mediated neuroprotection might be attributable to its anti-inflammatory actions through PPAR-γ activation.

Salvia miltiorrhiza (SM) has been used in oriental medicine for its neuroprotective effects against cardiovascular diseases and ischemic stroke. In this study, we investigated the therapeutic mechanism underlying the effects of SM on stroke using a transient middle cerebral artery occlusion (tMCAO) mouse model. Our results showed that SM administration significantly attenuated acute brain injury, including brain infarction and neurological deficits, 3 days after tMCAO. This was confirmed by our magnetic resonance imaging (MRI) study, which revealed a reduction in brain infarction with SM administration, as well as our magnetic resonance spectroscopy (MRS) study, which demonstrated the restoration of brain metabolites, including taurine, total creatine, and glutamate. The neuroprotective effects of SM were associated with the reduction in gliosis and upregulation of inflammatory cytokines, such as interleukin-6 (IL-6) and Tumor necrosis factor-α (TNF-α), along with the upregulation of phosphorylated STAT3 in post-ischemic brains. SM also reduced the levels of 4-Hydroxynonenal (4-HNE) and malondialdehyde (MDA), which are markers of lipid peroxidation, induced by oxidative stress upregulation in the penumbra of the tMCAO mouse brain. SM administration attenuated ischemic neuronal injury by inhibiting ferroptosis. Additionally, post-ischemic brain synaptic loss and neuronal loss were alleviated by SM administration, as demonstrated by Western blot and Nissl staining. Moreover, daily administration of SM for 28 days after tMCAO significantly reduced neurological deficits and improved survival rates in tMCAO mice. SM administration also resulted in improvement in post-stroke cognitive impairment, as measured by the novel object recognition and passive avoidance tests in tMCAO mice. Our findings suggest that SM provides neuroprotection against ischemic stroke and has potential as a therapeutic agent.

Prunus persica (L.) Batsch is a deciduous fruit tree cultivated worldwide. The flower of P. persica (PPF), commonly called the peach blossom, is currently consumed as a tea for weight loss in East Asia; however, its anti-obesity effects have yet to be demonstrated in vitro or in vivo. Since PPF is rich in phytochemicals with anti-obesity properties, we aimed to investigate the effects of PPF on obesity and its underlying mechanism using a diet-induced obesity model. Male C57BL/6 mice were fed either normal diet, high-fat diet (HFD), or HFD containing 0.2% or 0.6% PPF water extract for 8 weeks. PPF significantly reduced body weight, abdominal fat mass, serum glucose, alanine transaminase and aspartate aminotransferase levels, and liver and spleen weights compared to the HFD control group. Real-time quantitative polymerase chain reaction analysis revealed that PPF suppressed lipogenic gene expression, including stearoyl-CoA desaturase-1 and -2 and fatty acid synthase, and up-regulated the fatty acid β-oxidation gene, carnitine palmitoyltransferase-1, in the liver. Our results suggest that PPF exerts anti-obesity effects in obese mice and these beneficial effects might be mediated through improved hepatic lipid metabolism by reducing lipogenesis and increasing fatty acid oxidation.

Osteoarthritis (OA) is an age-related joint disease and one of the most common degenerative bone diseases among elderly people. The currently used therapeutic strategies relying on nonsteroidal anti-inflammatory drugs (NSAIDs) and steroids for OA are often associated with gastrointestinal, cardiovascular, and kidney disorders, despite being proven effective. Aucklandia lappa is a well-known traditional medicine. The root of A. lappa root has several bioactive compounds and has been in use as a natural remedy for bone diseases and other health conditions. We evaluated the A. lappa root extracts on OA progression as a natural therapeutic agent. A. lappa substantially reduced writhing numbers in mice induced with acetic acid. Monosodium iodoacetate (MIA) was injected into the rats through their knee joints of rats to induce experimental OA, which shows similar pathological characteristics to OA in human. A. lappa substantially reduced the MIA-induced weight-bearing of hind limb and reversed the cartilage erosion in MIA rats. IL-1β, a representative inflammatory mediator in OA, was also markedly decreased by A. lappa in the serum of MIA rats. In vitro, A. lappa lowered the secretion of NO and suppressed the IL-1β, COX-2, IL-6, and iNOS production in RAW264.7 macrophages activated with LPS. Based on its analgesic and anti-inflammatory effects, A. lappa could be a potential remedial agent against OA.

Osteoarthritis (OA) is characterized by irreversible joint destruction, pain, and dysfunction. Piper longum L. [Piperaceae] (PL) is an East Asian herbal medicine with reported anti-inflammatory, analgesic, antioxidant, anti-stress, and anti-osteoporotic effects. This study aimed to evaluate the efficacy of PL in inhibiting pain and progressive joint destruction in OA based on its anti-inflammatory activity, and to explore its potential mechanisms using in vivo and in vitro models of OA. We predicted the potential hub targets and signaling pathways of PL through network analysis and molecular docking. Network analysis results showed that the possible hub targets of PL against OA were F2R, F3, MMP1, MMP2, MMP9, and PTGS2. The molecular docking results predicted strong binding affinities for the core compounds in PL: piperlongumine, piperlonguminine, and piperine. In vitro experiments showed that PL inhibited the expression of LPS-induced pro-inflammatory factors, such as F2R, F3, IL-1β, IL-6, IL-17A, MMP-1, MMP-2, MMP-3, MMP-9, MMP-13, NOS2, PTGS2, PGE2, and TNF-β. These mechanisms and effects were dose-dependent in vivo models. Furthermore, PL inhibited cartilage degradation in an OA-induced rat model. Thus, this study demonstrated that multiple components of PL may inhibit the multilayered pathology of OA by acting on multiple targets and pathways. These findings highlight the potential of PL as a disease-modifying OA drug candidate, which warrants further investigation.