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.

Traditional Eastern Medicine (TEM) has a long history in stroke therapy and its therapeutic efficacy has been confirmed by clinical studies. Extensive experience and abundant clinical data on TEM in stroke treatment have been accumulated over the past thousand years. Basic and clinical research in TEM constitutes a potentially rich source for new drug discovery and development with the integration of TEM and Western pharmacology. In recent years, many attempts have been made to document research data from extracts of composite formulas, single herbs, or single compounds from TEM herbs, according to orthodox pharmacological actions. This article reviews herbs and prescriptions that have been documented to have a neuroprotective effect in in vitro and in vivo ischemic model systems, and the neuroprotective compounds isolated from them. I also discuss the neuroprotective mechanisms of prescriptions, herbs, and single compounds relevant to the treatment of brain ischemia, including anti–oxidant, anti–excitotoxic, and anti–inflammatory effects.

Dried roots of the plants Acanthopanax senticosus, Angelica sinensis and Scutellaria baicalensis are used in traditional oriental medicine and reportedly possess anti-inflammatory properties. Using the murine air pouch model of inflammation, we investigated the efficacy and mode of action of an extract from these three plants in crystal-induced inflammation. Air pouches were raised on the backs of 8-week-old BALB/c mice. Mice were fed 100 mg/kg body weight of root extracts (A. senticosus:A. sinensis:S. baicalensis mixed in a ratio of 5:4:1 by weight) or vehicle only on days 3–6. Inflammation was elicited on day 6 by injecting 2 mg of monosodium urate (MSU) crystals into the pouch. Neutrophil density and IL-6 and TNF-α mRNA levels were determined in the pouch membrane, and the leukocyte count and IL-6, prostaglandin E₂ (PGE₂) and prostaglandin D₂ (PGD₂) levels were determined in the pouch exudate. Treatment with the root extracts led to a reduction in all inflammatory parameters: the leukocyte count in the pouch exudate decreased by 82%; the neutrophil density in the pouch membrane decreased by 68%; IL-6 and TNF-α mRNA levels in the pouch membrane decreased by 100%; the IL-6 concentration in the pouch fluid decreased by 50%; and the PGE₂ concentration in the pouch fluid decreased by 69%. Remarkably, the concentration of the potentially anti-inflammatory PGD₂ rose 5.2-fold in the pouch exudate (p < 0.005), which led to a normalization of the PGD₂:PGE₂ ratio. A 3.7-fold rise in hematopoietic PGD synthase (h-PGDS) mRNA paralleled this rise in PGD₂ (p = 0.01).Thus, the root extracts diminished MSU crystal-induced inflammation by reducing neutrophil recruitment and expression of pro-inflammatory factors and increasing the level of the potentially anti-inflammatory PGD₂. These results support a need for further studies of the efficacy of these extracts in the treatment of inflammatory arthropathies and suggest elevation of PGD₂ levels as a novel mechanism for an anti-inflammatory agent.

Inulae Flos, the flower of Inula britannica L., is used as a dietary supplement, beverage, and medicine in East Asia. In this study, we evaluated the gastroprotective effects of Inulae Flos extract (IFE) against gastric mucosal lesions induced by hydrochloric acid (HCl)/ethanol in rats and explored its potential mechanisms by measuring antioxidant enzyme activity, mucus secretion, and prostaglandin E₂ (PGE₂) levels. Pretreatment with IFE at doses of 100 and 300 mg/kg significantly inhibited gastric lesions in HCl/ethanol-treated rats. IFE increased the activities of superoxide dismutase and catalase and the levels of glutathione and PGE₂ in gastric tissues. The administration of IFE also significantly increased the gastric wall mucus contents in HCl/ethanol-induced gastric lesions. These findings suggest that IFE has gastroprotective effects against HCl/ethanol-induced gastric lesions and exerts these effects through increased antioxidant levels and gastric mucus secretion. Inulae Flos may be a promising agent for the prevention and treatment of gastritis and gastric ulcers.

Polygonum cuspidatum is widely used as food and medicine in Korea, China, and Japan. Its major bioactive components, resveratrol and emodin, reportedly protect against gastric lesions. We therefore aimed to investigate: (1) the gastroprotective effects of P. cuspidatum roots in hydrochloric acid/ethanol (HCl/EtOH)- and indomethacin-induced acute gastric ulcer rat models; (2) the healing effects in an acetic acid-induced ulcer model; and (3) potential mechanisms by measuring gastric acid secretion-related parameters in a pyloric ligation-induced ulcer model, and by measuring antioxidant enzyme and prostaglandin E₂ levels in the gastric tissue of HCl/EtOH-treated rats. Oral administration of P. cuspidatum extract (PCE) at doses of 100 and 300 mg/kg significantly decreased HCl/EtOH- and indomethacin-induced gastric lesions. PCE at 300 mg/kg significantly reduced gastric lesions in acetic acid-induced ulcers. PCE increased superoxide dismutase (SOD) activity and glutathione (GSH) and prostaglandin E₂ levels in gastric tissue, whereas it did not alter gastric acid secretion-related parameters. Our findings indicate that PCE has gastroprotective effects against HCl/EtOH and non-steroidal anti-inflammatory drugs (NSAIDs) and promotes healing of acetic acid-induced ulcers. These gastric mucosal protection and ulcer healing effects are associated with antioxidant effects and the augmentation of prostaglandin E₂ and suggest that P. cuspidatum might be a promising preventive and therapeutic agent for treating gastric ulcers.