Trihydroxyxanthones from the heartwood of Maclura cochinchinensis modulate M1/M2 macrophage polarisation and enhance surface TLR4.

The anti-inflammatory actions of phytochemicals have attracted much attention due to the current state of numerous inflammatory disorders. Thai traditional medicine uses Maclura cochinchinensis (Lour.) Corner to treat chronic fever and various inflammatory diseases, as well as to maintain normal lymphatic function. Five flavonoids and five xanthones were isolated from the heartwood of M. cochinchinensis and we investigated the anti-inflammatory properties of the isolated compounds. All isolated compounds possessed an anti-inflammatory effect by decreasing prostaglandin E2 (PGE2) synthesis in lipopolysaccharide (LPS)-activated murine macrophages with varying degrees of potency. The greatest decrease in M1 inflammatory mediators, nitric oxide, PGE2, and proinflammatory cytokines was observed with 1,3,7-trihydroxyxanthone and 1,3,5-trihydroxyxanthone treatment of LPS-activated macrophages. The anti-inflammatory mechanism of the two xanthones is mediated by the suppression of inducible nitric oxide synthase, cyclooxygenase-2, and phosphatidylinositol 3-kinase/protein kinase B expression and the upregulation of M2 anti-inflammatory signalling proteins phosphorylated signal transducer and activator of transcription 6 and peroxisome proliferator-activated receptors-γ. 1,3,7-Trihydroxyxanthone exhibits superior induction of anti-inflammatory M2 mediator of LPS-activated macrophages by upregulating arginase1 expression. Following the resolution of inflammation, the two xanthones enhanced surface TLR4 expression compared to LPS-stimulated cells, possibly preserving macrophage function. Our research highlights the role of the two xanthones in modulating the M1/M2 macrophage polarisation to reduce inflammation and retain surface TLR4 once inflammation has been resolved. These findings support the use of xanthones for their anti-inflammatory effects in treating inflammatory dysregulation.

Model yeast as a versatile tool to examine the antioxidant and anti-ageing potential of flavonoids, extracted from medicinal plants.

The demand for the production of herbal extracts for cosmetics, food, and health supplements, known as plant-based medicine, is rising globally. Incorporating herbal extracts could help to create higher value products due to the functional properties of bioactive compounds. Because the phytochemical composition could vary depending on the processing methods, a simple bioassay of herbal bioactive compounds is an important screening method for the purposes of functional characterization and quality assurance. As a simplified eukaryotic model, yeast serves as a versatile tool to examine functional property of bioactive compounds and to gain better understanding of fundamental cellular processes, because they share similarities with the processes in humans. In fact, aging is a well-conserved phenomenon between yeast and humans, making yeast a powerful genetic tool to examine functional properties of key compounds obtained from plant extracts. This study aimed to apply a well-established model yeast, Saccharomyces cerevisiae, to examine the antioxidant and anti-aging potential of flavonoids, extracted from medicinal plants, and to gain insight into yeast cell adaptation to oxidative stress. Some natural quercetin analogs, including morin, kaempferol, aromadendrin, and steppogenin, protected yeast cells against oxidative stress induced by acetic acid, as shown by decreased cell sensitivity. There was also a reduction in intracellular reactive oxygen species following acetic acid treatment. Using the chronological aging assay, quercetin, morin, and steppogenin could extend the lifespan of wild-type S. cerevisiae by 15%-25%. Consistent with the fact that oxidative stress is a key factor to aging, acetic acid resistance was associated with increased gene expression of TOR1, which encodes a key growth signaling kinase, and MSN2 and MSN4, which encode stress-responsive transcription factors. The addition of the antioxidant morin could counteract this increased expression, suggesting a possible modulatory role in cell signaling and the stress response of yeast. Therefore, yeast represents a versatile model organism and rapid screening tool to discover potentially rejuvenescent molecules with anti-aging and anti-oxidant potential from natural resources and to advance knowledge in the molecular study of stress and aging.

Morin Attenuated Cerebral Ischemia/Reperfusion Injury Through Promoting Angiogenesis Mediated by Angiopoietin-1-Tie-2 Axis and Wnt/ß-Catenin Pathway.

Cerebral damage following cerebral ischemia/reperfusion injury affects the neurological deficits and motor impairment of stroke patients in the long-term period. Angiogenesis, the essential process for restoration of cerebral blood flow (CBF) in the ischemic brain, promotes the recovery of neurological function following ischemia. The aim of this study was to investigate the long-term effects of morin on angiogenesis and functional outcomes in a middle cerebral artery occlusion (MCAO) and reperfusion model. Male Wistar rats were subjected to MCAO, and they were administered 30 mg/kg of morin at reperfusion via i.p. injection daily for 14 days. Fourteen days after I/R injury, the rats were evaluated for the brain damage, and angiogenic factors involved in Ang1/Tie-2 and Wnt/ß-catenin signaling. In addition, at 1, 7, and 14 days after reperfusion, rotarod and pole tests were performed to investigate the functional recovery. We found morin significantly reduced the infarct size, blood-brain barrier (BBB) leakage, and apoptotic cells at 14 days after I/R injury. It also promoted angiogenesis via boosting the expression of angiogenic proteins, such as angiopoietin 1 (Ang1), Tie-2, Wnt3α, ß-catenin, and cyclin D1. Morin-mediated angiogenesis was confirmed by a significant increase in microvessel's density in the penumbra area and an increase in von Willebrand factor (vWF) protein expression of the morin-treated rats. Moreover, the rotarod and pole tests also demonstrated morin increased functional recovery in the morin-treated rats compared to the vehicle rats. Therefore, our data exposed that morin promotes angiogenesis and improves functional outcomes in MCAO and reperfusion rats.

Morin protects the blood-brain barrier integrity against cerebral ischemia reperfusion through anti-inflammatory actions in rats.

This study aimed to investigate the effects of morin on cerebral damage and blood-brain barrier (BBB) integrity in a middle cerebral artery occlusion (MCAO) and reperfusion model. Wistar rats were exposed to MCAO for 2 h, followed by reperfusion. Thirty mg/kg of morin was administered via intraperitoneal injection at the different time points: before ischemia, during ischemia, and at reperfusion. The rats were divided into five groups, including sham, vehicle, and three groups of morin. Twenty-four hours after reperfusion, the rats were tested for neurological deficits, and the brains were harvested to assess brain damage. In addition, brains were harvested 72 h to determine BBB disruption. We found that morin significantly reduced reactive oxygen species production and lipid peroxidation. It also decreased inflammation via reducing the expression of Toll-like receptor 4, nuclear factor kappa-beta. Morin ameliorated cerebral damage and reduced apoptosis through decreasing the cerebral infarct size, including apoptotic cell death. Moreover, morin decreased the BBB damage via reducing Evans blue extravasation, neutrophil infiltration, and increasing tight junction protein expression. Therefore, morin protected against cerebral and BBB damage by attenuating oxidative stress, inflammation, and apoptosis in MCAO and reperfusion models.